BIOMD0000000425
type: SBMLModel
reaction: metaid_0000008
is described by: http://identifiers.org/pubmed/23047527
reaction: metaid_0000006
reaction: metaid_0000005
occurs in: http://identifiers.org/taxonomy/562
volume units: volume
creator:
  ORG:
    orgname: Carnegie Mellon University
  n:
    given: Cheemeng
    family: Tan
species: metaid_0000004
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
is: MODEL1208300000
length unit: length
notes: Tan2012 - Antibiotic Treatment, Inoculum Effect The efficacy of many antibiotics decreases with increasing bacterial density, a phenomenon called the ‘inoculum effect’ (IE). This study reveals that, for ribosome-targeting antibiotics, IE is due to bistable inhibition of bacterial growth, which reduces the efficacy of certain treatment frequencies. This model is described in the article: The inoculum effect and band-pass bacterial response to periodic antibiotic treatment. Tan C, Phillip Smith R, Srimani JK, Riccione KA, Prasada S, Kuehn M, You L. Mol Syst Biol. 2012 Oct 9; 8:617 Abstract: The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes. This model is hosted on BioModels Database and identified by: MODEL1208300000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Dom…
compartment: metaid_0000003
name: Tan2012 - Antibiotic Treatment, Inoculum Effect
modified:
  W3 CDTF: Mon Jun 10 12:46:09 BST 2013
created:
  W3 CDTF: Thu Nov 01 15:23:56 GMT 2012
substance units: substance
is version of: GO:0071236
time units: time
curated: true
area units: area
reaction: metaid_0000007

metaid_0000008
type: Reaction
kinetic law: 177253
modifier: 432660
reactant: 177241
fast: false
reversible: false
name: reaction_4

177291
type: LocalParameter
notes: gamma represents the bacterial density
value: 1.0E-5
name: gamma

177279
type: LocalParameter
notes: the parameter delta lumps the effects of multiple reactions: it increases with decreasing rates of intrinsic or antibiotic-induced degradation of C (ribosomes), increasing dissociation between the antibiotic and C, and increasing export rate of the antibiotic.
value: 1.0E-5
name: delta

177266
type: LocalParameter
notes: phi represents the applied anitbiotic concentration
value: 5.0E-6
name: phi

metaid_0000004
type: Species
notes: c represents concentration of ribosomes C
has only substance units: false
in compartment: metaid_0000003
has part: P0A7L0
constant: false
has part: P0AG67
name: ribosome concentration
boundary condition: false
initial amount: 1.0
initial concentration: NaN

metaid_0000003
type: Compartment
is version of: GO:0005623
constant: true
size: 1.0
spatial dimensions: 3.0
name: cell

177241
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000004

metaid_0000006
type: Reaction
kinetic law: 177180
modifier: 432636
reactant: 177167
fast: false
reversible: false
name: reaction_3

177192
type: LocalParameter
value: 1.0
name: kd

177167
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000004

metaid_0000005
type: Reaction
kinetic law: 177142
product: 177130
fast: false
reversible: false
name: reaction_1

177155
type: LocalParameter
notes: alpha represents the basal synthesis rate of c
value: 0.001
name: alpha

177130
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000004

metaid_0000007
type: Reaction
kinetic law: 177217
modifier: 432648
product: 177204
fast: false
reversible: false
name: reaction_2

177229
type: LocalParameter
notes: kappa represents the concentration of c rliciting half-maximal activation of its positive feedback
value: 0.5
name: kappa

177204
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000004